Dissecting the role of VAP-1 in innate immune cell responses in the establishment and progression of liver disease (360G-Wellcome-203824_Z_16_A)

Liver disease is the third commonest cause of premature death in the UK and while recent advances in treatment of patients have shown promise, transplantation frequently remains the only treatment option for advanced disease (cirrhosis). This places a huge burden on health care systems worldwide, driven by the increasing frequency of liver injury due to alcohol or obesity. Our laboratories have shown that a molecule called Vascular Adhesion Protein-1 (VAP-1) contributes to the development of liver disease by reducing the function of the organ, and that the levels of VAP-1 in a blood sample can predict patient survival. Drugs that target VAP-1 have been developed and it is hoped that we can use therapies such as these to treat patients with not only liver disease, but also diseases in other organs and cancer. We propose to study how VAP-1 controls the migration of blood cells into and within the liver environment, using sophisticated models of liver disease and cutting-edge imaging and analysis techniques with donated human liver tissue. A better understanding of these processes will allow us to tailor drug treatment strategies for many patients and improve their chances of recovery from life-threatening illness.